期刊
BRITISH JOURNAL OF CANCER
卷 114, 期 2, 页码 151-162出版社
SPRINGERNATURE
DOI: 10.1038/bjc.2015.429
关键词
biomarker; blood; diagnosis; germ-cell tumour; microRNA; paediatric; relapse; serum
类别
资金
- CwCUK/GOSHCC
- SPARKS
- AstraZeneca
- CRUK
- MRC
- Erasmus MC MRACE grant
- Max Williamson Fund
- Perse Preparatory School, Cambridge
- Great Ormond Street Hospital Childrens Charity [W1058] Funding Source: researchfish
- Medical Research Council [MC_U105359875, MC_EX_G0800464] Funding Source: researchfish
- Sparks Charity [11CAM01] Funding Source: researchfish
- MRC [MC_EX_G0800464, MC_U105359875] Funding Source: UKRI
Background: The current biomarkers alpha-fetoprotein and human chorionic gonadotropin have limited sensitivity and specificity for diagnosing malignant germ-cell tumours (GCTs). MicroRNAs (miRNAs) from the miR-371-373 and miR-302/367 clusters are overexpressed in all malignant GCTs, and some of these miRNAs show elevated serum levels at diagnosis. Here, we developed a robust technical pipeline to quantify these miRNAs in the serum and cerebrospinal fluid (CSF). The pipeline was used in samples from a cohort of exclusively paediatric patients with gonadal and extragonadal malignant GCTs, compared with appropriate tumour and non-tumour control groups. Methods: We developed a method for miRNA quantification that enabled sample adequacy assessment and reliable data normalisation. We performed qRT-PCR profiling for miR-371-373 and miR-302/367 cluster miRNAs in a total of 45 serum and CSF samples, obtained from 25 paediatric patients. Results: The exogenous non-human spike-in cel-miR-39-3p and the endogenous housekeeper miR-30b-5p were optimal for obtaining robust serum and CSF qRT-PCR quantification. A four-serum miRNA panel (miR-371a-3p, miR-372-3p, miR-373-3p and miR-367-3p): (i) showed high sensitivity/specificity for diagnosing paediatric extracranial malignant GCT; (ii) allowed early detection of relapse of a testicular mixed malignant GCT; and (iii) distinguished intracranial malignant GCT from intracranial non-GCT tumours at diagnosis, using CSF and serum samples. Conclusions: The pipeline we have developed is robust, scalable and transferable. It potentially promises to improve clinical management of paediatric (and adult) malignant GCTs.
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